The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein.
Serum mannan-binding protein (S-MBP), a lectin specific for mannose and N-acetylglucosamine, was documented to activate complement through the classical pathway. In this study, we examined the mechanism that initiates this activation. By a passive hemolysis test using sheep erythrocytes coated with yeast mannan, the activation of complement by human S-MBP was shown to proceed in the absence of C1q. The following binding studies using 125I-labeled C1r2s2 and C1s indicated that the activated form of C1r2s2 bound to S-MBP located on the surface of the cells with high affinity. The binding of C1s to the cell-bound S-MBP require the presence of C1r, suggesting that C1r2s2 binds to S-MBP through C1r. The activation of C1s from a proenzyme to a protease was mediated by cell-bound S-MBP in the presence of C1r and the activated protease remained associated with the cells and was not released into the medium. The activation of complement with S-MBP was a solid phase event and did not proceed in a fluid phase. On the basis of these results, it was concluded that S-MBP is responsible for the initiation of carbohydrate-mediated complement activation as C1q does in immune complex-mediated complement activation.
Ohta
M
M
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Okada
M
M
Yamashina
I
I
Kawasaki
T
T
D000818:Animals; D002352:Carrier Proteins / Q000097:blood* / Q000302:isolation & purification; D037222:Collectins; D003167:Complement Activation; D015922:Complement C1q / Q000378:metabolism; D015923:Complement C1r / Q000378:metabolism; D003171:Complement Pathway, Classical; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D008351:Mannans / Q000097:blood* / Q000494:pharmacology; D012756:Sheep
D002352:Carrier Proteins; D037222:Collectins; D008351:Mannans; D015922:Complement C1q; D015923:Complement C1r